Project Summary/Abstract United States military Veterans from recent conflicts are coping with symptoms related to posttraumatic stress disorder (PTSD). Many Veterans are resistant to conventional health and mental health interventions (e.g., medication, psychotherapy), and often symptoms are not significantly improved by traditional treatments. Alternative treatment methods are needed. An underlying feature of PTSD is exaggerated inflammation, both peripherally and in the central nervous system, which is thought to play an important role in the vulnerability to, aggravation of, and perpetuation of adverse consequences of this condition. Therefore, an innovative intervention strategy would be the use of anti-inflammatory/immunoregulatory probiotics to reduce inflammation. In this study, we will investigate the effects of an 8-week oral administration of Lactobacillus rhamnosus GG (LGG; ATCC53103), a probiotic shown to have anti-inflammatory and immunoregulatory effects on both biological signatures of systemic inflammatory processes and proximal signatures of probiotic administration. LGG is a commensal organism that colonizes the human gut mucosa and suppresses mucosal inflammation via inhibition of the production of proinflammatory cytokines. The specific aim of the study is to identify the effect of probiotics on systemic inflammation, as well as PTSD symptoms, microbiota composition, gut permeability, stress response, and decision-making. Outcomes will be assessed using a longitudinal, double blind, randomized placebo-controlled design. After initial evaluation procedures to confirm PTSD and Functional Bowel Disorder diagnoses, 59 participants will be randomized to probiotic supplementation and 59 will be randomized to placebo supplementation. The proposed line of research addresses the NIH funding opportunity purpose, ?to accelerate translational and clinical Phase IIa? trials regarding ?probiotic[s]? to increase ?understanding regarding underlying mechanisms of their action(s), and variability in responses to these interventions?. Long-term, this study may lead to a paradigm shift in the manner by which we target clinical symptoms associated with PTSD by beginning the process of supporting a multitargeted, neuroprotective approach.